Neurofibromatosis is an autosomal dominant genetic disorder. It encompasses a set of distinct genetic disorders that cause tumors to grow along types of nerves and, in addition, can affect the development of non-nervous tissues such as bones and skin. The tumors can grow anywhere on or in the body. Apart from the common form, there are two rarer forms and several even rarer forms. Neurofibromatosis type I (was known as Von Recklinghausen disease after Friedrich Daniel von Recklinghausen) has an incidence of 1:3500. Neurofibromatosis type II (or “MISME Syndrome”) has an incidence of 1:40,000.
Schwannomatosis is a rare form that is clinically and genetically distinct from types I and II. Multiple Schwannomas (rather than Neurofibromas) occur, and about one-third of patients have these tumors in only one part of the body. Incidence is 1:40,000. The vestibular nerve is spared. Pain is the primary symptom, although numbness, tingling and weakness can also occur. Schwannomas are always benign. Additionally, six other, extremely rare, forms are also recognized but won't be discussed here.
Symptoms of these Diseases
Neurofibromatosis type 1, is a mutation of neurofibromin chromosome 17q11.2. Symptoms include multiple neurofibromas on the skin and under the skin, the sub-cutaneous lumps are characteristic of the disease and increase in number with age; freckling of the groin and the arm pit; a predisposition to particular tumors (both benign and malignant); Café au lait spots (pigmented birthmarks). Six or more of these symptoms form one of the diagnostic criteria, but are not essential for diagnosis. Skeletal abnormalities such as scoliosis or bowing of the legs might occur. Also occurring are Lisch nodules (hamartomas of iris), tumor on the optic nerve and plexiform neurofibroma. Neurofibromatosis type 2, caused by mutation of merlin chromosome 22q12.
Other symptoms include bilateral tumors; acoustic neuromas on the vestibulocochlear nerve, as the hallmark of NF 2 is hearing loss due to acoustic neuromas around the age of twenty. The tumors may cause headache, balance problems, and Vertigo, facial weakness/paralysis. Patients with NF2 may also develop other brain tumors, as well as spinal tumors, deafness and tinnitus. Schwannomatosis, the gene involved has yet to be identified.
Multiple Schwannomas occur. The Schwannomas develop on cranial, spinal and peripheral nerves. Chronic pain is present, and sometimes numbness, tingling and weakness. About ⅓ of patients have segmental Schwannomatosis, which means that the Schwannomas are limited to a single part of the body, such as an arm, a leg or the spine. Unlike the other forums of NF, the Schwannomas do not develop on vestibular nerves, and as a result, no loss of hearing is associated with Schwannomatosis. Patients with Schwannomatosis do not have learning disabilities related to the disease.
Neurofibromatosis type 1 is due to mutation on chromosome 17q11.2, the gene product being Neurofibromin (a GTPase activating enzyme). Neurofibromatosis type 2 is due to mutation on chromosome 22q, the gene product is Merlin, a cytoskeletal protein. Both NF1 and NF2 are autosomal dominant disorders, meaning that only one copy of the mutated gene need be inherited to pass the disorder. A child of a parent with NF1 or NF2 and an unaffected parent will have a 50% chance of inheriting the disorder.
Complicating the question of heritability is the distinction between genotype and phenotype, that is, between the genetics and the actual manifestation of the disorder. In the case of NF1, no clear links between genotype and phenotype have been found, and the severity and specific nature of the symptoms may vary widely among family members with the disorder. In the case of NF2, however, manifestations are similar among family members; a strong genotype-phenotype correlation is believed to exist. Both NF1 and NF2 can also appear spontaneously through random mutation, with no family history. These spontaneous or sporadic cases account for about one half of neurofibromatosis cases.